The invention relates to compositions for the treatment or prevention of viral infection. The invention also relates to compositions for the treatment of tumors.
Illnesses resulting from viral infection remain as a major problem to be addressed by modern medicine. To date, there is no 100% effective treatment for infection with any known virus. Recently there has been progress towards treatment of several viral diseases, but these treatments are largely directed at specific viruses or classes of viruses. For example, protease inhibitors targeting the virally-encoded human immunodeficiency virus (HIV) protease have been effective against some strains of HIV, and have been responsible, when used in combination with other anti-viral agents, for a decline in HIV-related deaths in the United States. However, the protease inhibitors are specific for specific viruses or classes of viruses, and are not useful for the treatment of viruses outside of those classes. In addition, there is evidence that strains resistant to these new agents are evolving.
It is noted that the virus-specific agents currently being used in developed countries are very expensive, being beyond the means of a great number of infected individuals throughout the world. In addition, the dosage regimens are complex and demand careful attention by physicians and the infected individuals.
Because viruses co-opt the host""s own normal intracellular metabolic processes for their reproductive needs, a major difficulty in the design of antiviral agents is to make agents that target the virus without toxicity to the host organism.
There is a need in the art for antiviral agents that are effective against a broad spectrum of viruses, relatively non-toxic, inexpensive to produce, and simple to administer.
Many of the same problems plaguing those attempting to develop antiviral therapies are faced by those wishing to cure cancer. Transformed cancer cells share the same cellular metabolic processes as non-transformed cells, differing primarily in a loss of normal growth control. Therefore, it has been difficult to develop treatment strategies that are effective against tumor cells without significant toxicity to non-tumor cells. There is a need in the art for effective anti-tumor therapies that minimize the toxicity to non-transformed cells and tissues.
The invention relates to methods and compositions for treating the symptoms of viral infection and for reducing the size or cellular load of a tumor.
More specifically, the invention encompasses a composition comprising the chemical compounds of Structure Nos. 1-4 and analogs thereof with antiviral activity. The invention also encompasses a composition consisting essentially of any one or a combination of the chemical compounds of Structure Nos. 1-4. The invention also encompasses a composition comprising at least 10%, 20%, 50%, 75%, 90%, 95% or 99% of any one or a combination of structures 1-4 by weight. Structures 1 and 2 are chiral, as are structures 3 and 4. A composition of the invention may have relative amounts of (Structures 1 and 2): (Structures 3 and 4) in proportions ranging from 1:100, 1:10, 1:1, 10:1, or even 100:1.
The invention also encompasses an antiviral composition comprising a mixture of zinc oxide, aspartic acid, and high fructose corn syrup.
In one embodiment, the composition comprising a mixture of zinc oxide, aspartic acid, and high fructose corn syrup comprises one mass unit of zinc oxide, about 2.5 mass units of aspartic acid, and about 64.5 mass units of high fructose corn syrup.
The invention further encompasses an antiviral composition consisting essentially of a mixture of zinc oxide, aspartic acid and high fructose corn syrup.
In a preferred embodiment, the high fructose corn syrup has the following characteristics: a) about 77% solids and about 23% moisture; and b) a carbohydrate composition as follows: about 55% fructose; about 41% dextrose; the remainder being higher saccharides. In another embodiment, pure fructose (i.e., a composition consisting essentially of fructose), or a composition comprising about 96% fructose and 4% higher polysaccharides, is used in the preparation of an antiviral composition of the invention.
The invention further encompasses a method of making an antiviral or antitumor composition, such method comprising the steps of: a) combining zinc oxide, aspartic acid and high fructose corn syrup to form a mixture; b) heating the mixture until visible insoluble material is absent; and c) dehydrating the resulting composition to less than or equal to 1.5% water.
In a preferred embodiment of the method, the step of heating comprises the sequential steps of: a) heating the mixture to 170xc2x0 F. for 10 minutes; b) heating the mixture to 180xc2x0 F. for 15 minutes; and c) heating the mixture to 190xc2x0 F. for 3 to 5 hours, until no insoluble material is visible to the naked eye.
In a preferred embodiment of the method, the mixture of step (a) comprises one mass unit of zinc oxide, about 2.5 mass units of aspartic acid, and about 64.5 mass units of high fructose corn syrup.
In a further preferred embodiment of the method, the high fructose corn syrup has the following characteristics: a) about 77% solids and 23% moisture; and b) a carbohydrate composition as follows: about 55% fructose, about 41% dextrose, with the remainder being higher saccharides.
The invention further encompasses a method of reducing the duration of symptoms of viral infection, the method comprising the step of administering a therapeutically effective amount of a composition comprising a chemical compound selecting form the group consisting of structures 1-4 or an analog thereof having antiviral activity, such that the duration of the symptoms is reduced.
In a preferred embodiment, the virus is one which causes the common cold.
In another preferred embodiment, the virus is herpes zoster (varicella zoster).
The invention further encompasses a method of reducing the titer of a virus in a virally infected individual, the method comprising the step of administering a therapeutically effective amount of a composition comprising, selected from the group consisting of structure 1-4 an analog thereof, such that the titer of the virus in the individual is reduced.
The invention further encompasses a method of increasing the number of CD4+ T cells in an individual infected with human immunodeficiency virus, the method comprising the step of administering a therapeutically effective amount of a composition selected from the group consisting of structure 1-4 an analog thereof, such that the number of CD4+ T cells is increased.
The invention further encompasses a method of maintaining the number of CD4+ T cells in an individual infected with human immunodeficiency virus, the method comprising the step of administering a therapeutically effective amount of a composition selected from the group consisting of structure 1-4 an analog thereof, such that the number of CD4+ T cells is maintained.
The invention further encompasses a method of reducing the size of a tumor in an individual, the method comprising the step of administering a therapeutically effective amount of a composition selected from the group consisting of structure 1-4 an analog thereof, such that the size of the tumor is reduced.
In preferred embodiments of the methods of reducing the duration of symptoms of viral infection, reducing the titer of a virus, increasing or maintaining CD4+ T cells, or reducing the size or cellular load of a tumor, the composition is administered transmucosally.
In other preferred embodiments of the methods of reducing the duration of symptoms of viral infection, reducing the titer of a virus, increasing or maintaining CD4+ T cells, or reducing the size or cellular load of a tumor, the composition is administered parenterally.
The invention further encompasses a kit for performing the methods of reducing the duration of symptoms of viral infection, reducing the titer of a virus, increasing or maintaining CD4+ T cells, or reducing the size or cellular load of a tumor.
As used herein, the term xe2x80x9cantiviral activityxe2x80x9d refers to the ability of a composition or treatment regimen to ameliorate the symptoms of a viral infection. Intiviral activity includes, but is not limited to an activity resulting in a reduction by at least 10% in viral titer or a reduction by at least 10% in the severity or duration of the symptoms of a viral infection. The symptoms of a viral infetion include not only those directly caused by viral replication and accompanying cell death, but also secondary symptoms, such as those caused by opportunistic bacterial infections that occur subsequent to the death of infected cells.
As used herein, the term xe2x80x9canalogxe2x80x9d refers to a composition that varies from an original or primary composition by the presence of one or more chemical additions, deletions or substititions not present in the structure of the primary composition. An analog as used herein will have at least 50% of the antiviral or antitumor activity of the primary composition, and preferably more, up to and exceeding 100% of the activity of the primary composition. An analog may have physical or functional characteristics that differ from those of the primary composition, for example, different or enhanced solubility, membrane permeability, or biological half-life, while retaining anti-viral or anti-tumor activity. The term xe2x80x9canalogxe2x80x9d also refers to a different enantiomeric form of a given compound, such as the dextrorotatory or levorotatory form of a molecule or a compound made using one or another enantiomeric forms of a given constituent. As a non-limiting example, the compositions made by mixing the D, or L enantiomeric forms of aspartic acid with zinc oxide and high fructose corn syrup as described herein would be considered analogs of the composition made using the mixed enantiomeric D+L form of aspartic acid.
As used herein, the term xe2x80x9chigh fructose corn syrupxe2x80x9d refers to a liquid carbohydrate composition comprising at least 50% fructose by weight. The carbohydrate composition is preferably derived from corn or other vegetable or plant material. The remaining proportion may contain various relative amounts of other saccharides, including, but not limited to sucrose, dextrose and higher saccharides.
As used herein, the phrase xe2x80x9cmixture comprising zinc oxide, aspartic acid, and high fructose corn syrupxe2x80x9d means a combination comprising zinc oxide, the D, L, or D+L forms of aspartic acid, and high fructose corn syrup meeting the definition of high fructose corn syrup presented herein.
As used herein, the term xe2x80x9csolidsxe2x80x9d refers to the matter present after the removal of water or solvent, such as by lyophilization or evaporation.
As used herein, the term xe2x80x9ccarbohydrate compositionxe2x80x9d refers to a mixture consisting essentially of of higher and lower saccharides. Higher saccharides include those having more than two linked carbohydrate monomers or subunits, for example, trisaccharides (three monomer subunits), tetrasaccharides (four monomer subunits) or oligosaccharides with more than four carbohydrate subunits. Lower saccharides include those with one or two carbohydrate monomers. A carbohydrate composition may initially be in the form of a solid or powdered solid, or it may initially be in the form of a liquid solution.
As used herein, the term xe2x80x9cvisible insoluble materialxe2x80x9d refers to particles of material in a solution that are visible to the naked eye, assuming natural or corrected 20/20 vision. A visible insoluble material may include particulate matter that settles near the bottom of a container holding a solution, or it may include fine particulate matter that remains in suspension but reduces the transparency of the solution. A solution or mixture with no visible insoluble material may be colored, but will be transparent, with no visually observable cloudiness.
As used herein, the term xe2x80x9cdehydratingxe2x80x9d refers to a process whereby water is removed from a solution or composition. According to the invention, dehydrating may be accomplished by processes including, but not limited to, freeze-drying (lyophilization), dessication under vacuum with or without heating, or dessication at atmospheric pressure with heating. A dehydrated composition of the invention will have about 5% or less, preferably about 2.5%, 1.5%, 1%, 0.5%, 0.2%, 0.1% or less of water by weight.
As used herein, the term xe2x80x9creducing the duration of symptomsxe2x80x9d means that the length of time symptoms of a viral infection are present is lessened by at least 10% in a treated individual relative to an individual receiving no treatment. The time or duration of symptoms of a viral infection is the time from which symptoms first become apparent to the infected individual until such symptoms are not apparent to the same individual (i.e., symptoms are fully resolved).
As used herein, the term xe2x80x9cadministeringxe2x80x9d refers to a process whereby a composition of the invention is introduced to the body of an individual in need of treatment. Administration may, for example, be by way of absorption through oral or other (e.g., rectal or vaginal) mucosa (referred to herein as xe2x80x9ctransmucosalxe2x80x9d delivery or administration. Alternatively, administration may be by intramuscular, intravenous or intraperitoneal delivery means, which are collectively referred to herein as xe2x80x9cparenteralxe2x80x9d administration or delivery. Topical administration, for example for the treatment of shingles, or other viral infection affecting the skin, is not excluded from the meaning of xe2x80x9cadministeringxe2x80x9d presented herein.
As used herein, the term xe2x80x9ctherapeutically effective amountxe2x80x9d refers to the amount of a composition of the invention necessary to reduce the symptoms of a viral infection by at least 10%, to slow or halt the growth of a tumor, or to reduce the size of a tumor by at least 10%. A therapeutically effective amount may be delivered over a period of days, weeks or longer in order to have the desired therapeutic effect.
As used herein, the term xe2x80x9ccommon coldxe2x80x9d refers to the disease symptoms resulting from infection with members of the rhinovirus family. Symptoms can include any or all of sore throat, cough, nasal congestion, runny nose, sneezing, swollen glands, muscular achiness and fever.
As used herein, the term xe2x80x9creducingxe2x80x9d or xe2x80x9creducedxe2x80x9d when used to refer to the titer of a virus in an infected individual means that the titer of virus is lessened by at least 10%, and preferably by 20%, 30%, 50%, 70%, 90% or more, up to and including 100%. (i.e., no detectable virus present).
As used herein, the term xe2x80x9cmaintaining the number of CD4+ Txe2x80x9d cells refers to the situation in which treatment according to the invention results in no fluctuation (increase or decrease by up to 5%) in the number of CD4+ T cells in a given volume of peripheral blood over a period of at least one week. Preferably, CD4+ T cell counts are maintained for months or even years or decades following commencement of treatment.
As used herein, the term xe2x80x9cincreasing the number of CD4+ Txe2x80x9d cells refers to the situation in which treatment according to the invention results in an increase in the number of CD4+ T cells relative to the number of CD4+ T cells present prior to the commencement of treatment, with the increase being at least 5%, and preferably as much as 10%, 20%, 30%, 50%, 75%, or even 100% or more, up to and surpassing 500 CD4+ T cells per microliter of blood.
As used herein, the term xe2x80x9cHuman Immunodeficiency Virusxe2x80x9d or xe2x80x9cHIVxe2x80x9d is meant to refer to all strains of human immunodeficiency. viruses. Active human immunodeficiency virus infection results in a decline in the number of CD4+ T cells, which in turn results in the incapacity of the infected individual to mount an effective immune response to viral, bacterial, fingal or parasitic infections.
As used herein, the term xe2x80x9creducing the size of a tumor in an individualxe2x80x9d means that the size of a solid tumor or the load of tumor cells from a non-solid malignancy (e.g., a leukemia) is decreased by at least 10% or more, preferably as much as 20%, 30%, 50%, 70%, 90%, or even up to and including 100% decreased (i.e., no tumor or tumor cells) relative to the tumor size or tumor cell number before treatment according to the invention.
Further features and advantages of the invention will become more fully apparent in the following description of the embodiments and drawings thereof, and from the claims.